Grant 46

Research Institution: Nationwide Children’s Hospital

Principle Investigator:

Associate Professor Scott Harper

Type: International - Ohio, USA

Project title: “Developing a systemic myostatin-inhibiting gene therapy approach to improve muscle weakness in a new FSHD mouse model”

Status: Active


Our goal is to improve muscle function in FSHD patients by developing an AAV.Follistatin gene therapy strategy to inhibit myostatin (molecule that inhibits muscle cell growth). We have already demonstrated proof-of-principle for this approach using intramuscular injection in our new TIC-DUX4 FSHD mouse model. Administering AAV.Follistatin significantly improved muscle size and overall force production when delivered locally to TIC-DUX4 tibialis anterior and gastrocnemius muscles. A systemic delivery approach would potentially achieve widespread coverage of nearly all muscles, and therefore offer the broadest possible benefit of myostatin inhibition therapy. Indeed, this is consistent with the goals of another Phase II clinical trial currently being conducted, where a ligand trap, follistatin-derived molecule is being administered systemically to patients with FSHD. The major difference with our approach, if successful, will be that it only requires only a single treatment, rather than repeated doses.